The paper reports the profile of impairment across a variety of cognitive functions with special emphasis on tests sensitive to frontal lobe dysfunction, in 24 elderly depressed patients during and ...on recovery from mood disorder, compared with 15 age- and sex-matched controls. Traditional neuropsychological tests and a recently developed battery of computerized tests (CANTAB) were used. Impairments were found in the depressed group compared to controls and to themselves on recovery across all domains examined. The depressed group showed deficits on visuospatial recognition memory, attentional shifting at the extra-dimensional shift stage and in measures of both processing and motor speed without impaired accuracy in a visual search task. Impairments were also found on a planning task with disproportionately increased numbers of moves needed for more difficult problems and evidence of both slowed motor response and increased processing time once the task was commenced. Performance on recovery improved across all tasks. Comparisons were made with the performance of patients suffering from dementia of the Alzheimer type (DAT) and Parkinson's disease on similar tests. Response latencies in test performance were found to correlate with the number of episodes of depression suffered and with ventricular size on CT scan, as measured by computerized planimetry. On recovery, residual depression scores correlated with latency of test performance and with ventricular brain ratio. The results, thus, show that depression in the elderly is associated with a significant degree of deficit on tests sensitive to frontostriatal dysfunction. Some of the deficits appear specific to depression and some do not remit following clinical recovery. However, these impairments have to be interpreted in the context of a broad profile of cognitive deficit.
Using quantitative autoradiography of 3Hforskolin we have visualized the activated states of adenylate cyclase in the hippocampal formation bilaterally in sections from schizophrenic brain and ...age-matched controls. There is a generalized increase in binding in schizophrenic hippocampi, particularly in the CA1 region and parahippocampal gyrus. The effect is particularly marked in the left parahippocampal gyrus. These findings add some support to the notion of schizophrenia as a medial temporal lobe disorder and suggest novel substrates as therapeutic targets in schizophrenia.
Sleeping with the bed-head raised is commonly recommended as treatment for patients with troublesome oesophagitis, but its effect has not been objectively tested. Ranitidine therapy is useful in ...oesophagitis, but it does not often produce complete relief of symptoms. The effects of each of these treatments alone and in combination have been studied in 71 patients with severe (grade III) peptic oesophagitis. Each treatment improved both symptoms and endoscopic appearances significantly more than placebo did. However, the combination of the two treatments was much better than either alone; the reduction in pain score and the area of ulceration healed were about twice those with either treatment alone. Smoking more than five cigarettes per day or drinking more than 30 g alcohol per day significantly reduced the effectiveness of ranitidine therapy, but age, sex, body weight, or the presence of a hiatus hernia had no detectable effect.
Systemic immune cell dynamics during coronavirus disease 2019 (COVID-19) are extensively documented, but these are less well studied in the (upper) respiratory tract, where severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2) replicates
. Here, we characterized nasal and systemic immune cells in individuals with COVID-19 who were hospitalized or convalescent and compared the immune cells to those seen in healthy donors. We observed increased nasal granulocytes, monocytes, CD11c
natural killer (NK) cells and CD4
T effector cells during acute COVID-19. The mucosal proinflammatory populations positively associated with peripheral blood human leukocyte antigen (HLA)-DR
monocytes, CD38
PD1
CD4
T effector (T
) cells and plasmablasts. However, there was no general lymphopenia in nasal mucosa, unlike in peripheral blood. Moreover, nasal neutrophils negatively associated with oxygen saturation levels in blood. Following convalescence, nasal immune cells mostly normalized, except for CD127
granulocytes and CD38
CD8
tissue-resident memory T cells (T
). SARS-CoV-2-specific CD8
T cells persisted at least 2 months after viral clearance in the nasal mucosa, indicating that COVID-19 has both transient and long-term effects on upper respiratory tract immune responses.
Abstract SARS-CoV2 infection results in a range of disease severities, but the underlying differential pathogenesis is still not completely understood. At presentation it remains difficult to ...estimate and predict severity, in particular, identify individuals at greatest risk of progression towards the most severe disease-states. Here we used advanced models with circulating serum analytes as variables in combination with daily assessment of disease severity using the SCODA-score, not only at single time points but also during the course of disease, to correlate analyte levels and disease severity. We identified a remarkably strong pro-inflammatory cytokine/chemokine profile with high levels for sCD163, CCL20, HGF, CHintinase3like1 and Pentraxin3 in serum which correlated with COVID-19 disease severity and overall outcome. Although precise analyte levels differed, resulting biomarker profiles were highly similar at early and late disease stages, and even during convalescence similar biomarkers were elevated and further included CXCL3, CXCL6 and Osteopontin. Taken together, strong pro-inflammatory marker profiles were identified in patients with COVID-19 disease which correlated with overall outcome and disease severity.
Heart Rate versus Heart Rate Variability.
Introduction: The aim of this study was to evaluate and compare heart rate and heart rate variability (HRV) in risk prediction after acute myocardial ...infarction (MI) and to evaluate the effect of beta‐blocker treatment on the prognostic performance of heart rate and HRV.
Methods and Results: Three hundred sixty‐six patients underwent 24‐hour Holter recording 1 to 6 days after an MI. HRV was expressed as the standard deviation of all normal‐to‐normal intervals. Left ventricular systolic function was evaluated using the wall motion index. Half of the patients were taking a beta‐blocker at the time of Holter recording. Mean follow‐up was 44 months (median 34) after MI. By the end of follow‐up, 82 patients had died. Mortality at 1 and 3 years was 12.5% and 22.6%, respectively. HRV, heart rate, wall motion index, number of ventricular premature beats per hour, and ventricular tachycardia were all significantly (P < 0.05) associated with mortality in univariate analysis, independent of beta‐blocker therapy. In multivariate Cox analysis, only heart rate, wall motion index, number of ventricular premature beats per hour, and age had independent prognostic value (P < 0.001). In any model, including heart rate, HRV had no predictive value.
Conclusion: The prognostic information of HRV is contained completely in heart rate, which carries prognostic information further than that of HRV. This result was independent of beta‐blocker treatment. (J Cardiovasc Electrophysiol, Vol. 14, pp. 168‐173, February 2003)
An open letter to the President Appleby, L.; Lewis, G.; Cawley, R. H. ...
Psychiatric bulletin of the Royal College of Psychiatrists,
12/1988, Volume:
12, Issue:
12
Journal Article
An open letter to the President Appleby, Louis; Lewis, Glyn; Cawley, R. H. ...
Psychiatric bulletin of the Royal College of Psychiatrists,
12/1988, Volume:
12, Issue:
12
Journal Article
MxA is a GTPase encoded by an interferon-inducible human gene. Its constitutive expression renders transfected mammaliancells resistant to infections with several different RNA viruses, including ...vesicular stomatitis virus (VSV). Differences in viral RNA levels of VSV-infected cells either expressing or lacking MxA indicated that VSV mRNA synthesis is the principal target of MxA action. We now used purified histidine-tagged MxA (His-MxA) that we produced in
Escherichia coli to successfully inhibit VSV
in vitro transcription, a reaction catalyzed by VSV ribonucleoprotein complexes isolated from virus-infected cells or from purified virions. MxA was inactive when added to preformed VSV mRNAs, arguing against the possibility that it has a negative effect on viral RNA stability. MxA inhibited both leader RNA and mRNA synthesis of VSV, suggesting that it interfered with transcription initiation. The degree of VSV inhibition correlated directly with the specific GTPase activities of the various wild-type MxA preparations. No inhibition of viral mRNA synthesis was observed when a C-terminally truncated, GTPase-inactive variant of His-MxA was added to the transcription reactions. Purified His-MxA-E645R, a mutant of MxA with normal GTPase activity whose range of antiviral activity
in vivo is altered so that it no longer inhibits VSV, showed no inhibitory effect on VSV
in vitro transcription. Since MxA inhibited VSV RNA synthesis in the presence of GMP-PNP or GTP
γS, GTP analogs that are readily accepted by the viral polymerase but cannot be hydrolyzed by MxA, the possibility was excluded that MxA acts by depleting the viral polymerase for its nucleotide substrates. Thus, binding of GTP rather than its hydrolysis seems of importance for the anti-VSV activity of MxA.
PDF
